The aim of this proposal is to study the mechanisms of the anticarcinogenic effects of carotenoid pigments. In particular, many of the experimental protocols are designed to answer the question as to whether carotenoids have effects on induction or promotion of carcinogenesis. To achieve this aim, whole animal studies will be carried out using either 7, 12-dimethybenz(a)anthracene (DMBA) or UV-B (290-320 nm) as the initiator, followed by treatment with a promoter, 12-0-tetradecanoyl-phorbol-13-acetate (TPA). By altering carotenoid treatment of the animals, it should be possible to determine if the reported effects of carotenoids on preventing either DMBA or UV-B initiated skin tumors reflects an action at the level of the initiation or promotion process. Of particular interest will be our use of carotenoids which are not provitamins A (canthaxathin, crocetin, phytoene), therefore, eliminating any possibility that the anticarcinogenic action is due to conversion of the carotenoids to vitamin A. In addition, we will use a similar approach in attempting to dissect the mechanism of carotenoid action in cell cultures. Syrian Hamster Embryo cells and Chinese hamster ovary cells all respond to either carcinogens or to TPA. Experimental protocols are described which will enable us to determine if the carotenoids display antimutagenic properties in these cells, and if these effects are related to the initiation process or to the promotion process. Finally, we will examine the effects of carotenoid pigments in terms of their ability to modify or inhibit the actions of promoters in either human polymorphonuclear leukocytes (PMN) or human platelets. Both cell types respond to promoters, and retinoids have already been used to block these effects in PMN. Our long-term objectives are to define the mechanisms whereby carotenoids exert an anticarcinogenic effect. By so doing, we will be in a position to offer substantial scientific data to support the hypothesis that dietary carotenoids might alter cancer incidence rates. Due to their low toxicity and ready availability, carotenoids have the potential, if their mechanisms are verified, of making a significant contribution to the potential control of cancer.